title: Negative parafibromin staining predicts malignant behavior in atypical parathyroid adenomas.
abstract: BACKGROUND
  The histopathological criteria for carcinoma proposed by the World Health Organization (WHO) are imperfect predictors of the malignant potential of parathyroid tumors. Negative parafibromin (PF) and positive protein gene product 9.5 (PGP9.5) staining are markers of CDC73 mutation and occur commonly in carcinoma but rarely in adenomas. We investigated whether PF and PGP9.5 staining could be used to predict the behavior of atypical parathyroid adenomas--tumors with atypical features that do not fulfill WHO criteria for malignancy.
  
  
  METHODS
  Long-term outcomes were compared across four groups: group A, WHO-positive criteria/PF-negative staining; group B, WHO(+)/PF(+), group C; WHO(-)/PF(-); and group D, WHO(-)/PF(+).
  
  
  RESULTS
  Eighty-one patients were included in the period 1999-2012: group A (n = 13), group B (n = 14), group C (n = 21), and group D (n = 33). Mortality and recurrence rates, respectively, for group A were 15 and 38%, for group B 7 and 36%, for group C 0 and 10%, and for group D 0 and 0%. The PGP9.5(+) ratios for groups A to D were 85, 78, 71, and 12%, further informing prognosis. Five-year disease-free survival for groups A to D were 55, 80, 78, and 100%, respectively. Tumor recurrence was significantly associated with PF (p = 0.048) and PGP9.5 (p = 0.003) staining.
  
  
  CONCLUSIONS
  Although WHO criteria are essential to differentiate parathyroid carcinoma from benign tumors, the presence of negative PF staining in an atypical adenoma predicts outcome better, whereas PF-positive atypical adenomas do not recur and can be considered benign. PF-negative atypical adenomas have a low but real recurrence risk and should be considered tumors of low malignant potential.
authors.affiliation: Endocrine Surgical Unit, University of Sydney, Sydney, NSW, Australia, kruijffs@gmail.com.
authors.forename: Schelto
authors.initials: S
authors.lastname: Kruijff
authors.forename: Stan B
authors.initials: SB
authors.lastname: Sidhu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sywak
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.forename: Leigh W
authors.initials: LW
authors.lastname: Delbridge
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D009367:Neoplasm Staging; D010281:Parathyroid Hormone / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D013194:Staining and Labeling; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C454900:CDC73 protein, human; D010281:Parathyroid Hormone; D025521:Tumor Suppressor Proteins; D002118:Calcium